While protein-protein interactions in cell recognition have been recognized for some time, only recently has the role of carbohydrates in physiologically relevant recognition been widely considered (See Brandley, B. K., and Schnaar, R. L., J. Leuk. Biol. (1986) 40:97; and Sharon, N., and Lis, H., Science (1989) 246:227). Oligosaccharides are well positioned to act as recognition molecules due to their cell surface location and structural diversity. Many oligosaccharide structures can be created through the differential activities of a smaller number of glycosyltransferases. Their diverse structures, then, can be generated with relatively few gene products, suggesting a plausible mechanism for establishing the information necessary to direct a wide range of cell-cell interactions. Examples of differential expression of cell surface carbohydrates and putative carbohydrate binding proteins (lectins) on interacting cells have been described (see Dodd, J., and Jessel, T. M., J. Neurosci. (1985) 5:3278; Regan, L. J., et al., Proc. Natl. Acad. Sci. USA (1986) 83:2248; Constantine-Paton, M., et al., J. Biol. Chem. (1986) 324:459; and Tiemeyer, M., et al., J. Biol. Chem. (1989) **3**, 1671). Further, the question has been raised as to what is the leukocyte receptor for ELAM-1 (See Bevilacqua et al. Proc Natl. Acad. Sci. USA (1987) 84:9238).
Glycolipids have been identified in fetal tissue and a variety of human cancers, including CML cells (Fukuda, M. N., et al., J. Biol. Chem. (1986) 261:2376;Magnani, J. L., et al., J. Biol. Chem. (1982) 257:14365; Hakomori, S., et al., Biochem. Biophys. Res. Comm. (1983) 113:791), and are designated as sialyl-Le.sup.x structures. This has led to the hypothesis that these structures may be important in many developmental and oncogenic processes (J. L. Magnani et al., J. Biol. Chem. (1982) 257:14365). Smaller quantities of most of these carbohydrates can be found in normal human tissue (see Fukushi, Y., et al., J. Exp. Med. (1984) 160:506), but until now no function for these structures has been reported.
Adhesion of circulating neutrophils to stimulated vascular endothelium is a primary event of the inflammatory response. Several receptors have been implicated in this interaction, including a family of putative lectins that includes gp90.sup.MEL (Leu8), GMP-140 (PADGEM) and ELAM-1 (Gong, J.-G., et al., Nature (1990) 343:757; Johnston, G. I., et al., Cell (1989) 56:1033; Geoffroy, J. S., and Rosen, S. D., J. Cell Biol. (1989) 109:2463; Lasky, L. A., et al., Cell (1989) 56:1045). While these receptors each contain a domain with sequence homology to calcium dependent lectins, only gp90.sup.MEL has been demonstrated to recognize a carbohydrate (See J. S. Geoffrey et al., J Cell Biol. (1989) 109:2463). Endogenous ligands for these receptors have yet to be identified.
ELAM-1 is particularly interesting because of its transient expression on endothelial cells in response to IL-1 or TNF (Bevilacqua, M. P., et al., Science (1989) 243:1160). The time course of this induced expression (2-8 h) suggests a role for this receptor in initial neutrophil extravasation in response to infection and injury. Furthermore, Bevilacqua et al. (see Bevilacqua, M. P., et al., Proc. Natl. Acad. Sci. USA (1987) 84:9238) have demonstrated that human neutrophils or HL-60 cells will adhere to COS cells transfected with a plasmid containing a cDNA encoding for the ELAM-1 receptor. The present inventors have now found that ELAM-1 recognizes a carbohydrate present on a subset of structurally related acidic glycolipids isolated from human leukocytes and developed the present invention.